Catalyst-free hierarchical reduction of CO₂ with BH₃N(C₂H₅)₃ for selective N-methylation and N-formylation of amines

Highlights

• Catalyst-free methodology for N-formylation and N-methylation of amines using BH₃N(C₂H₅)₃ and CO₂.

• Good to excellent yields of methylamines and formamides are obtained.

• CO₂ was activated by inserting into B–H bonds of BH₃N(C₂H₅)₃.

Abstract

We describe herein an efficient and catalyst-free methodology for N-formylation and N-methylation of various amines using BH₃N(C₂H₅)₃ as a reductant and CO₂ as C1 source. This system is compatible with a wide range of substrates, such as aromatic secondary amines, aliphatic secondary amines, heterocyclic amines, and primary amines. The desired methylamines and formamides are obtained in excellent yields by changing the reaction solvent, temperature, and the amount of BH₃N(C₂H₅)₃. The optimum yields of methylamines and formamides are up to 99 %, which are comparable to the data using different catalysts. Moreover, it has been demonstrated by mechanistic research that CO₂ was activated by inserting into B–H bonds of BH₃N(C₂H₅)₃ and formamide can be regarded as an intermediate species during the N-methylation formation.

Introduction

Formamides are widely used in chemical industrial syntheses. It can be regarded not only as the key intermediates in the synthesis of isocyanates [[1], [2], [3]], medicines [[4], [5], [6], [7]], and pesticides [[8], [9], [10]], but also as solvents in organic synthesis reactions such as N,N-dimethylformamide or N,N-dimethylacetamide [[11], [12], [13]]. Traditionally, formamides synthesis through an N-formylation reaction requires the using of highly toxic CO as a carbonylation reagent to react with amines [14]. Methylamines play the significant role in the fabrication of natural products and cancer detection [[15], [16], [17]]. Methylamines are commonly acquired through amine methylation reaction in which dimethyl carbonate [[18], [19], [20]], methanol [[21], [22], [23]], and formaldehyde [[24], [25], [26]] can be used as the methylation reagents. In contrast, a green and more attractive strategy to produce methylamine or formamide had been explored in which CO₂ reacts with amines through N-methylation and N-formylation reactions.

CO₂, a most representative greenhouse gas, is still recognized as a green, cheap, and the world's most abundant C1 resource, which has been used extensively in organic synthesis, serving as a promoter, mediator, or catalyst [[27], [28], [29], [30]]. It is well known that the transformation of CO₂ is challenging due to its inherent thermodynamic stability and kinetic inertia [[31], [32], [33]]. Hence, highly active reductants such as hydrosilanes and borohydrides are widely used in the N-methylation and N-formylation reactions. Particularly, when H₂ is used as a reductant, the crucial point of this procedure is the accurate activation of both inert CO₂ and H₂ molecules simultaneously. It has been reported that metal catalysts showed significant activity using H₂ as reductant, such as Ru [34,35], Pd [36,37], Au [38,39], Cu [40,41], Fe [42], and Co [43]. However, these reactions needed to occur under the conditions of high pressure and temperature, and the scope of substrate application was limited. There are many studies reported that N-formylation and N-methylation of amines can be well controlled by utilizing hydrosilanes or borohydrides as reductants [[44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55]]. In 2017, Dyson et al. [44] reported that an N-heterocyclic carbene catalyst can efficiently motivate N-formylation and N-methylation under mild conditions. Whereafter, He et al. [[45], [46], [47]] has been successively established betaine, K₂WO₄, and copper catalysis system showing prominent activity in the N-methylation and N-formylation selectivity with hydrosilane as the reductant. Almost simultaneously, Xia and coworkers [48,49] sequentially reported that both DBU and iron catalyst can catalyze amines to produce the corresponding methylamines and formamides selectively. In addition, some solvent-switched and catalyst-free amines N-formylation and N-methylation had also been reported using borohydrides as the reductants [[56], [57], [58]]. Despite the above exciting results, using hydrosilanes or borohydrides as the reductant would lead to a comparatively low atomic economy. In particular, the recovery of the catalyst is not only difficult but also expensive. Recently, in the course of our study on the conversion of CO₂ [59,60], we have invested a lot of effort to selectively prepare methylamine, but only a few substrates can be compatible in the synthesis of methylamines in the moderate yields, presumably due to formamide cannot be further reduced to methylamine. Therefore, the development of the catalyst-free methodology to control the reaction of CO₂ with amine selective N-formylation and N-methylation using the same reductant is highly desirable.

Herein, we reported an efficient and catalyst-free hierarchical reduction of CO₂ with borane triethylamine [BH₃N(C₂H₅)₃] and amines to selectively produce formamides and methylamines. Only by changing the reaction solvent, temperature, and amount of BH₃N(C₂H₅)₃, the excellent yields of the target products methylamines or formamides can be attained, respectively. More exciting, up to 99 % yield can be obtained for both methylamines and formamides, which are comparable to the currently reported procedures using metal or metal-free catalysts (Table S1). Particularly, we found that formamide can be reduced to methylamine using reductant of BH₃N(C₂H₅)₃. This straightforward and efficient methodology had potential application in the synthetic chemistry.